This invention relates to the healing of bone and connective tissues.
Growth factors are polypeptide hormones which stimulate a defined population of target cells. Examples of growth factors include platelet-derived growth factor (PDGF), insulin-like growth factors (IGF-I and II), transforming growth factor beta (TGF-.beta.), epidermal growth factor (EGF), and fibroblast growth factor (FGF). PDGF is a cationic, heat-soluble protein found in the granules of circulating platelets which is known to stimulate in vitro protein synthesis and collagen production by fibroblasts. It is also known to act as an in vitro mitogen and chemotactic agent for fibroblasts, smooth muscle cells, and glial cells.
It has been proposed to use PDGF to promote in vivo soft tissue wound healing. For example, Grotendorst (1984) J. Trauma 24:549-52 describes adding PDGF to Hunt-Schilling wire mesh chambers impregnated with a collagen gel and implanted in the backs of rats; PDGF was found to increase the amount of new collagen synthesized. However, Leitzel et al., (1985) J. Dermatol. Surg. Oncol. 11:617-22 were unable to accelerate normal wound healing in hamsters using PDGF alone or in combination with FGF and EGF.
Michaeli, et al. (1984) In Soft and Hard Tissue Repair (Hunt, T.K. et al., Eds), Praeger Publishers, New York, pp. 380-394, report that application of a partially purified preparation of PDGF obtained from platelet-rich plasma stimulated angiogenesis when implanted in rabbit corneas. Because PDGF is not an angiogenic growth factor the investigators suggested that an unknown factor in their partially purified PDGF preparation was responsible for the angiogenic effect.
Canalis (1985) Clin. Orthoped. Rel. Res. 193: 246-263 reports that PDGF stimulates DNA synthesis and non-specific protein synthesis in calvariae in organ culture. In contrast, Tashijian, et al. (1982), Endocrinology 111:118 report that PDGF is a potent inducer of bone resorption in mouse calveria cultures. PDGF-stimulated bone resorption was mediated through increased prostaglandin production.